The research proposed in this application is designed to determine the roles of a variety of cellular and humoral factors in effecting immunologically mediated tissue destruction in vivo. Special emphasis is placed on the vulnerability of tumor grafts to humoral and cellular antibodies at various times after the grafts have been placed in subcutaneous or intraperitoneal sites. Attempts will be made to determine in each case those effector substances whose concentrations or availabilities tend to limit the rate or intensity of tissue damage. This will entail the isolation and purification of various specific and non-specific mediators of tissue damage, including NK cells, and the evaluation of their roles, alone or in combination, in the production of damage in vivo. It is intended that this information will facilitate the development of more effective forms of cancer immunotherapy. It should also icrease significantly our understanding of mechanisms of tissue damage in other disease states and in rejection of normal tissue grafts.